The medial preoptic area (MPOA) is an important node for several social behaviors, including male and female sexual behaviors and maternal behavior. Perhaps the best predictor of a male rat's ability to copulate is extracellular dopamine (DA) in his MPOA. The ability to intromit requires normal basal levels of MPOA DA, maintained by nitric oxide (NO) under the influence of estrogen. The ability to ejaculate is correlated with an increase in extracellular DA in response to a receptive female and during copulation; this increase requires androgen, as well as estrogen and NO. Glutamate elicits MPOA DA release, via NO, and is important for both sexual behavior and sexual learning. The proposed research will investigate the intra- and intercellular factors that govern MPOA DA and glutamate release and their consequences for performance and learning. In addition, the mesolimbic DA tract is critical for numerous motivated behaviors. Aim 1 will clarify the mechanisms of sexual learning, including whether previous sexual experience alters transmitter release in the MPOA, DA receptor density, numbers, or affinity, in the MPOA and mesolimbic tract, whether it alters phosphorylation of intracellular proteins in the MPOA, and whether repeated administration of DA and/or glutamate agonists mimic the effects of experience. Aim 2 expands our studies of hormonal regulation of MPOA function by testing whether steroid hormones influence glutamate and GABA release and whether they influence the expression, numbers, or affinity of DA receptors. Aim 3 will determine the neurotransmitter interactions in the MPOA that regulate copulation and sexual learning, including whether D2 DA receptors influence GABA or glutamate release and whether subtypes of DA receptors are located on neurons that contain NMDA glutamate receptors or GABA. Aim 4 will investigate the place of the MPOA within the broader network that regulates sexual and other social behaviors by determining the transmitter content of a major afferent to the MPOA and of a major efferent. Sexual experience not only renders mating more efficient but also protects it from the disruptive effects of stress and various lesions. DA and glutamate cooperate in several forms of learning, although the specific mechanisms may vary. This research will allow a comparison of the mechanisms of sexual learning with those of other forms of learning, including pair bond formation, parental behavior, and drug addiction. DA agonists and drugs that prolong NO's effects are major treatments for sexual dysfunction. Also, a major problem with antidepressant drugs is their inhibitory sexual side effects. This research will provide information that may improve these treatments. The proposed research will also integrate the MPOA into the broader neural network that regulates all social behaviors. A major problem with drug treatments for depression, psychosis, and anxiety is their inhibitory sexual side effects, which may lead the patient to discontinue the medication. In addition many men and women are distressed over their sexual dysfunction. The proposed research will delineate the neural mechanisms that control sexual function and should lead to new treatments for sexual dysfunction and potential single- or multi- drug treatments for psychological disorders that carry fewer sexual side effects. In addition, this research will provide insights into a form of learning in an "old" area of the brain, as well as in the network that mediates numerous motivated behaviors, including sexual and maternal behaviors, eating, pair bonding, and drug addiction. [unreadable] [unreadable] [unreadable]